DOES HLA-G14BP INS/DEL POLYMORPHISM INTERACT WITH POST TRANSPLANT RISK FACTORS?

Obesity, dyslipidemia, type 2 diabetes mellitus and arterial hyper- tension are known to be post-transplant medication-related risk factors in kidney transplantation. Associations exist between these disorders, in!ammation and immune function. Immunogenetic polymorphisms of molecules involved in allograft rejection or tolerance could also affect some of the most important cardiovascular and metabolic risk factors involved in post transplant outcome. HLA-G is a non classical HLA molecule with immunomodulant and immunosuppressive functions. We investigated if HLA-G14bp ins/del polymorphism in exon 8, previously studied in kidney allograft rejection with contro- versial results, could be involved in post transplant variations of body mass index (BMI) and other risk factors for late post transplant morbidity and mortality. Polymorphisms of some cytokines with both immunosuppressive and/or metabolic effects, or affecting HLA-G expression (IL-10-1082G/C, -819C/T, -592C/A, TGF-beta+869 T/G, +915C/G, IL-6-174G/C, IFN-gamma+874 T/A and TNF-alpha-308G/A) were also assessed for comparisons. Pre-post transplant BMI/obesity, lipid abnormalities and increased fasting plasma glucose were examined in association with genotypes in kidney transplant recipients from cadaveric donors (n=173). PCR and PCR-SSP techniques were used for analyses. Results showed a signi cant association of HLA-G14bp ins/ins genotype with post transplant obesity (three years after transplantation, p<0.001, OR=6.1, CI 2.4-15.4; 5 years, p=0.002, OR=3.7, CI 1.6-8.7). Effects of HLA-G14bp genotypes on post transplant BMI/obesity were con- rmed in multivariate analyses and in the subset of pre-transplant non-obese patients. Other cytokine genotypes did not associate with the examined factors. In conclusion, HLA-G14bp ins/del polymorphism, previously involved in transplantation for its tolerogenic activity, seems to have a potential impact on the development of obesity after kidney transplantation.